Disrupting fibrin sheath from a host blood vessel and visualization thereof

ABSTRACT

A percutaneous transluminal angioplasty (PTA) catheter may be configured to perform vein expansion and occlusion. A infusion port (132) located proximal to the occlusion feature (162) can be used to inject contract enhancement agent as well as other substances. The catheter can be used especially advantageously in vascular regions associated with hemodialysis access.

RELATED APPLICATIONS

This application is a U.S. National Stage Entry Under 35 U.S.C. 371 ofInternational Application No. PCT/IB2013/001895 filed on Jul. 8, 2013,which claims the benefit of priority under 35 U.S.C. § 119(e) from U.S.Provisional Patent Application No. 61/669,284 filed on Jul. 9, 2012;U.S. Provisional Patent Application No. 61/752,743 filed on Jan. 15,2013; and U.S. Provisional Patent Application No. 61/752,649 filed onJan. 15, 2013; the disclosures of which are incorporated herein byreference in their entireties.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to systemsand methods for treating blood vessels or grafts, and in particular todilatation balloon catheters for dilating and/or recanalizing occludedor narrowed vein portions and/or vascular accesses.

ESRD (end-stage renal disease) patients amount to about 3 millionworldwide, out of which approximately 2 million undergo periodichemodialysis treatments. Hemodialysis requires a vascular access, a siteon the body where blood is removed and returned during the dialysisprocess. The most common accesses are the arteriovenous (AV) fistula,and the AV graft. Complications of clogging and stenosis occur with highpercentages, causing low blood flow at the access site and risking thedialysis process. A regular checkup and assessment of the access isrequired. Once a problem of low blood flow is identified due to accessnarrowing, an angioplasty procedure is required to recover normal bloodflow. If a blood clot is occluding the access, commonly associated withsynthetic grafts, the treatments include thrombectomy and/orthrombolysis. Dialysis access procedures are performed several times perday per operator. Current techniques are time consuming and force themedical practitioner to extended exposures to x-ray radiation.

A venous flow obstruction or stenosis, commonly found in the graft-veinor vein-artery anastomosis of the arteriovenous fistula, causes slowdown or obstruction of blood flow, which may result in the formation ofthrombus within a graft. Stenotic vein portions may also be found atlocations remote from the anastomosis such as in the brachicephalicvein. Usually mechanical thrombolysis means and/or administration ofclot dissolving thrombolytic agents is used. After clot dissolution, thepatient is typically analyzed under fluoroscopic imaging of the graft toidentify and visualize residual venous stenosis. Angioplasty of thestenosed segment can then be performed, using dedicated high pressuredilatation balloon catheters, optionally followed with implanting astent in order to keep opened areas that are prone to restenosis.

The cephalic vein or basilic vein, which are most common in vascularrecanalization of hemodialysis accesses, are substantially largeconduits, usually 3 to 6 mm in diameter, demanding high pressuredilatations of 15 atmospheres or more, and in some instances require theuse of high pressure ultra-noncompliant dilatations of 25 atmospheres ormore. Therefore, specially designed and sized angioplasty or PTA ballooncatheters were developed for such specific indications, including, forexample, the Kevlar balloon based Conquest® PTA dilatation catheter (ofCR Bard; Covington, Ga.), provided in nominal inflation diametersbetween 5 mm and 12 mm, and with rated burst pressures between 20 atmand 30 atm.

Before and/or during the angioplasty procedure, blood thinners areadministrated to prevent formation of blood clots in the conduit duringprolonged angioplasty. The blood thinners in dialysis patients carry arisk of bleeding in different areas in the body including at the accesssites to the fistula or graft. Having the option to reduce or eliminatethe necessary dose of blood thinners will greatly improve patient safelyas well as operators' convenience and satisfaction. Less time will beneeded for hemostasis at the end of the procedure.

In order to position the balloon adjacent the stenosis and evaluate theresult of the angioplasty, a contrast medium is administered tofacilitate visualization under fluoroscopic imaging. In common practice,in order to administer the contrast medium adjacent the stenotic regionfollowing angioplasty, the dilatation balloon is withdrawn and isreplaced with an occlusion balloon for blocking unwanted flow directionof the contrast medium. An occlusion balloon, as opposed to a highpressure dilatation balloon, is made substantially compliant in order totake a shape according to local surrounding boundaries. Inventor MichaelTal in U.S. Pat. No. 7,182,755 “METHOD AND APPARATUS FOR TREATMENT OFTHROMBOSED HEMODIALYSIS ACCESS GRAFTS”, the disclosures of which isfully incorporated herein by reference, describes a balloon cathetercomprising “a catheter body with a compliant balloon secured at a distalend of the catheter body, a single aperture positioned proximally of theballoon, a first lumen extending through the catheter body and in fluidcommunication with the balloon for selectively inflating and deflatingthe balloon, and a second lumen extending through the catheter body andin fluid communication with the aperture for dispensing solutiontherethrough.”

The need to replace the angioplasty balloon with an occlusion balloonfor administering contrast medium is cumbersome and time consuming andeven less efficient if further dilatation sessions are needed. This isespecially important in angioplasty procedures involving the use ofdelivering or eluting drug with the angioplasty catheter, used forprevent or diminish restenosis in the recanalized vascular portion, withor without a stent deployed in-place, which usually involve repeated orcontinuous dilatation for prolonged durations greater than 1 minute, andmore commonly 3 minutes or more.

Problems associated with current vascular access recanalization thusinclude: use of multiple catheters and multiple device exchanges, eachassociated with additional radiation to visualize position of eachcatheter; rapid blood flow in the access limits visualization of theblood vessels and requires repeated contrast injections and angiograms;risk of clot migration to artery when performing de-clotting procedure.

There is thus a need to introduce multi-functional balloon cathetersdedicated to angioplasty and/or occlusion that also include means forfluids dispersion (medicaments and declotting agents, flushing mediaand/or contrast enhancing media) for facilitating improved techniquesthat can lower number of procedural steps, treatment time and radiationexposure. There is also a need to decrease overall amount of contrastenhancing media injected per session. There is also a need to injectcontrast enhancing media into a clogged access for whole accessvisualization while declotting, therefore diminishing the risk of clotmigration to the artery.

SUMMARY OF THE INVENTION

The present disclosure relates to dilatation balloon catheters such as aPTA (percutaneous transluminal angioplasty) balloon catheter, optionallyof a high pressure type, optionally introducible as an over the wirecatheter. The catheter possess the attribute of injecting fluid to thetreated site through a dedicated opening located proximally to theballoon member, for introduction of fluids such as contrast enhancingmaterial and/or medication. Fluid injection can be performedsimultaneously while inflating or deflating the balloon, or whileballoon is maintained inflated. Possibly, number of radiopaque markingsis present to define the working length of the balloon and facilitate inballoon placement. In some embodiments, a single lumen is used, at leastin part, both for fluids transfer and dispersion (“infusion”) as well asfor guide wire passage. In some such embodiments, a valve mechanism isused to sustain selective operability of the lumen so that fluids willdisperse mostly or solely through the proximal dispersion opening ratherthan the guide wire distal exit opening. In one example, the catheterends with a tip, optionally an atraumatic tip with a check-valveintegrated inside the guide wire lumen distal to the injection openingto allow infusion of fluids with or without the guide wire. Such adevice can be used for multiple function is sequence and/or in parallel,such as: performing high-pressure angioplasty in native arteriovenousdialysis fistulae or synthetic grafts; perform balloon dilatation andsimultaneous contrast material injection; using smaller amounts ofcontrast enhancing material; decreasing use of angiograms and radiationexposure to staff and patient.

Catheters according to the present disclosures may be used also forembolectomy and declotting procedures. A device according to the presentinvention may include, though not necessarily, a relatively soft andcompliant balloon fixed at the distal tip. The catheter possess theattribute of injecting fluid to the treated site through a dedicatedopening proximal to the balloon for introduction of fluids such as clotdissolving material (such as TPA). Fluid injection can be performedsimultaneously while inflating or deflating the balloon, or whileballoon is maintained inflated. Such a device can be used for multiplefunction is sequence and/or in parallel, such as: performing balloonocclusion (possibly following dilatation) and simultaneous clotdissolving fluid injection; reducing the risk of clot migration to thearterial side during thrombectomy procedure and injection of contrast tothe clogged access; using smaller amounts of contrast enhancingmaterial; decreasing use of angiograms and radiation exposure to staffand patient.

According to an aspect of some embodiments of the present inventionthere is provided a dilatation balloon catheter which comprises anexpandable chamber sized and configured to expand a vein lumen portionin a dialysis vascular access above a nominal size thereof. In some suchembodiments, the vein is a cephalic or basilica vein, and/or thevascular access is an arteriovenous graft or an arteriovenous fistula.In some such embodiments, the nominal size is at least 3 mm or at least10 mm. In some embodiments, the expandable chamber is configured tomaintain a non-ruptured form under inflation pressures exceeding 20atmospheres, in some embodiments exceeding 25 atmospheres. In someembodiments, such inflation pressures can be maintained continuously forat least 1 minute. This allows time, for example, for imaging a vascularregion associated with dialysis access while the dilatation balloonremains inflated.

In some embodiments, the expandable chamber comprises an inflatableballoon. The inflatable balloon may be configured to maintain anon-ruptured form under continuous and/or repeated expansions under theinflation pressures for at least 3 minutes.

In some embodiments, the dilatation balloon catheter further comprises aguidewire lumen for allowing a guidewire to pass therethrough and exitthrough a guidewire exit port located distally to the infusion exitport.

In some embodiments, the dilatation balloon catheter comprises aninfusion exit port located proximally to the expandable chamber forallowing a contrast enhancing fluid to exit the dilatation ballooncatheter.

In some embodiments, the dilatation balloon catheter further comprisesan infusion inlet port and an infusion lumen intercommunicating theinfusion inlet port and the infusion exit port, the infusion inlet portis connectable to communicate with an interior of an appendix reservoircontaining infusion material. The infusion material may comprise thecontrast enhancing fluid. Alternatively or additionally, the infusionmaterial may comprise at least one of: mitotic inhibitor, antimitoticagent, mitosis modulator, antineoplastic agent, antiproliferative agent,immunosuppressive agent, paclitaxel, sirolimus, zotarolimus, everolimus,Biolimus A9, anticoagulation agent and heparin. Alternatively oradditionally, the infusion material may comprise at least one of:antiproleferative agent solvent, Cremophor EL, castor oil, ethanol,albumin, protamine sulfate, antiproliferative agent enhancer,antibiotics, and a vitamin.

In some embodiments, the infusion inlet port is further connectable to asource for continuously flowable flushing fluid.

In some embodiments, the dilatation balloon catheter further comprises amedication dispersion lumen for allowing a medication to passtherethrough and exit through a medication exit port located adjacent tothe infusion exit port.

In some embodiments, the expandable chamber comprises a compliant layerexpandable to take a form constrained by surrounding boundaries of thevein lumen portion, readily expanded above the nominal size, and toocclude the lumen portion from the contrast enhancing fluid passingbetween periphery thereof and the surrounding boundaries. Optionally,alternatively or additionally, the expandable chamber comprises anon-compliant layer expandable to form the vein lumen portion to anexpanded size above the nominal size having predefined boundaries.

In some embodiments, the dilatation balloon catheter comprises a firstindependently inflatable balloon that includes a compliant layer and asecond independently inflatable balloon that includes a non-compliantlayer. In some embodiments, the expandable chamber comprises the secondindependently inflatable balloon and positioned proximally distanced tothe first independently inflatable balloon. Optionally andalternatively, the expandable chamber comprises the second independentlyinflatable balloon disposed within the first independently inflatableballoon.

In some embodiments, any of the compliant layer, the non-compliantlayer, the first independently inflatable balloon and the secondindependently inflatable balloon, are coated or impregnated with atleast one of mitotic inhibitor, antimitotic agent, mitosis modulator,antineoplastic agent, antiproliferative agent, immunosuppressive agent,paclitaxel, sirolimus, zotarolimus, everolimus, Biolimus A9,anticoagulation agent, and heparin.

In some embodiments, the expandable chamber further comprises anexpandable rigid spacer, optionally comprises a selectively expandablecage member, wherein the compliant layer is disposed between the spacerand the surrounding boundaries. In some such embodiments, the spacercomprises a self-expandable member provided in covering sheath, theself-expandable member is radially expandable when the covering sheathis proximally withdrawn.

In an aspect of some embodiments, there is provided a method whichcomprises at least one of the following steps, not necessarily in sameorder: inserting a dilatation balloon catheter in a narrowed vein lumenportion adjacent a dialysis vascular access through an opening in thedialysis vascular access; positioning the expandable chamberappositionally to the lumen portion; expanding the expandable chamber toexpand the lumen portion to above the nominal size; applying thedilatation balloon catheter to occlude the expanded lumen portion; andadministering contrast enhancing fluid through the infusion exit port.

Optionally, alternatively or additionally, the method comprises at leastone of the following steps, not necessarily in same order: inserting adilatation balloon catheter in a narrowed vein lumen portion of a nonmaturing fistula through an opening in the vein portion of the fistula;positioning the expandable chamber appositionally to the narrow segmentof the non maturing fistula; expanding the expandable chamber to expandthe lumen portion to above the nominal size; applying the dilatationballoon catheter to occlude the expanded lumen portion; infusingmedication into the narrowed segment through the balloon over aprolonged period of time; and administering fluid through the infusionexit port continuously for at least 1 minute.

In some embodiments, the applying is comprised in the expanding.

In some embodiments, the applying and/or expanding comprises inflatingthe first independently inflatable balloon.

In some embodiments, the inflating includes elevating a pressure in thefirst independently inflatable balloon to a maximal pressure being atleast 20 atmospheres, or in some cases at least 25 atmospheres. In somesuch embodiments, the maximal pressure is maintained and/or repeatedlyobtained for at least 1 minute. In some such embodiments, the firstindependently inflatable balloon is coated or impregnated with a firstanti-restenosis medication.

In some embodiments, the applying comprises expanding an expandablerigid spacer.

In some embodiments, the method further comprises: delivering a secondanti-restenosis medication through the infusion exit port.

In some embodiments, the first anti-restenosis medication and/or thesecond anti-restenosis medication comprises at least one of a mitoticinhibitor, an antimitotic agent, a mitosis modulator, an antineoplasticagent, an antiproliferative agent, an immunosuppressive agent,paclitaxel, sirolimus, zotarolimus, everolimus, Biolimus A9, ananticoagulation agent, and heparin.

In some embodiments, the method further comprises: flushing the narrowedvein lumen portion with a continuous stream of flushing fluid throughthe infusion exit port.

A variety of methods are also provided.

In one implementation, a method of visualizing a vessel segmentassociated with dialysis treatment comprises selecting a hemodialysispatient having a hemodialysis vascular access path and/or otherhemodialysis related vascular region in need of angiographicvisualization and/or angioplasty treatment, inserting a catheter in avessel of the selected hemodialysis patient, the catheter comprising anelongated shaft having an infusion lumen, an expandable dilatationchamber disposed on the elongated shaft, and one or more infusionopenings in communication with the infusion lumen positioned proximallyadjacent to the expandable dilatation chamber, positioning theexpandable dilatation chamber at a narrowed or obstructed lumen segmentat or near an arterial or venous anastomosis associated with anarteriovenous fistula and/or an arteriovenous graft, and expanding atleast the expandable dilatation chamber to expand the narrowed orobstructed lumen segment above its nominal size. Then, using the samealready inserted catheter, substantially occluding blood and other fluidflow through the expanded lumen segment, administering a radiographiccontrast enhancing agent through the one or more infusion openings whilemaintaining the substantially occluded blood and other fluid flow, andradiographically imaging the vascular region at and/or around thearteriovenous fistula and/or arteriovenous graft proximal to theexpanded lumen segment while maintaining the substantially occludedblood and other fluid flow.

In this implementation, the expandable dilatation chamber may comprisean inflatable balloon. The expandable dilatation chamber may beconfigured to maintain a non-ruptured state under a pressure of at least20 atmospheres. The expandable dilatation chamber may be configured tomaintain a non-ruptured state under a pressure of at least 20atmospheres for at least one minute. The expanded dilatation chamber mayperform both the expanding and the substantial occluding at the sametime. The substantially occluding may comprise occluding the expandedlumen segment at least 95%. The method may further comprise visualizingthe vascular region at and/or around the arteriovenous fistula and/orarteriovenous graft proximal to the expanded lumen segment withfluoroscopic imaging while the dilatation chamber remains expanded.Expanding the expandable dilatation chamber may comprise expanding anexpandable rigid spacer. The method may comprise expanding an occlusionballoon provided on the catheter that is separate from the dilatationchamber to perform the occluding. The occlusion balloon may beproximally adjacent to the dilatation chamber. The dilatation chambermay be inside the occlusion balloon. The catheter may include a singleinfusion opening.

In another implementation, a method of treating a narrowed vein adjacentan arteriovenous anastomosis comprises inserting a balloon catheter in avein lumen of a vein that is connected at an arteriovenous anastomosisto an artery, the balloon catheter comprising an elongated shaft havingan infusion lumen, and an expandable dilatation balloon disposed alongthe elongated shaft. The method may continue by advancing the ballooncatheter in the vein lumen toward the arteriovenous anastomosis untilthe expandable dilatation balloon reaches a narrowed vein segment,inflating the expandable dilatation balloon to open the narrowed veinsegment, maintaining inflation of the expandable dilatation balloon toocclude the vein segment for a prolonged period, such as at least 1minute for example, and administering a contrast enhancing fluid throughan exit port of the infusion lumen while the expandable dilatationballoon remains inflated.

In another implementation, a method of treating a narrowed vein spacedupstream from an arteriovenous anastomosis comprises inserting a ballooncatheter in a vein lumen of a vein that is connected at an arteriovenousanastomosis to an artery, the balloon catheter comprising an elongatedshaft having an infusion lumen, and an expandable dilatation balloondisposed along the elongated shaft. The method may continue by advancingthe balloon catheter away from the arteriovenous anastomosis until theexpandable dilatation balloon reaches a narrowed vein segment, inflatingthe expandable dilatation balloon to open the narrowed vein segment,maintaining inflation of the expandable dilatation balloon to occludethe vein segment for a prolonged period, and administering a contrastenhancing fluid through an exit port of the infusion lumen towards thearteriovenous anastomosis and into the artery while the expandabledilatation balloon remains inflated.

In another implementation a method of treating a narrowed vein adjacentan arteriovenous anastomosis comprises inserting a balloon catheter in avein lumen of a vein that is connected at an arteriovenous anastomosisto an artery, the balloon catheter comprising an elongated shaft havingan infusion lumen, and an expandable dilatation balloon disposed alongthe elongated shaft. The method may continue by advancing the ballooncatheter in the vein lumen toward the arteriovenous anastomosis untilthe expandable dilatation balloon reaches the arteriovenous anastomosis,inflating the expandable dilatation balloon at the arteriovenousanastomosis to block clotting material from entering the artery,maintaining inflation of the expandable dilatation balloon to occludethe arteriovenous anastomosis for a prolonged period, administering acontrast enhancing fluid through an exit port of the infusion lumenwhile the expandable dilatation balloon remains inflated, imaging thevein to locate blocked or narrowed vein lumen portions, and injecting aclot dissolving material through a portion of the balloon catheter andinto the vein lumen at a location proximal to the expandable dilatationballoon.

In another implementation, a method of recanalizing a blockedarteriovenous graft comprises inserting a balloon catheter in a graftlumen or in a vein lumen of a vein that is connected by a graft to anartery, the balloon catheter comprising an elongated shaft having aninfusion lumen, and an expandable dilatation balloon disposed along theelongated shaft. The method may continue by advancing the ballooncatheter away from a venous anastomosis until the expandable dilatationballoon reaches an arterial anastomosis, inflating the expandabledilatation balloon at the arterial anastomosis to block clottingmaterial from entering the artery, maintaining inflation of theexpandable dilatation balloon to occlude the arteriovenous anastomosisfor a prolonged period, administering a contrast enhancing fluid throughan exit port of the infusion lumen while the expandable dilatationballoon remains inflated, imaging the graft to locate blocked ornarrowed graft lumen portions, and injecting a clot dissolving materialthrough a portion of the balloon catheter and into the graft lumen andvein lumen at a location proximal to the expandable dilatation balloon.

In another implementation, a method of treating a fibrin sheathassociated with a long term implanted hemodialysis catheter comprisesselecting a hemodialysis patient having a hemodialysis catheterpositioned in a vascular access path extending along a jugular vein andthe superior vena cava, removing the implanted hemodialysis catheter,inserting a percutaneous transluminal angioplasty (PTA) catheter intothe vascular access path previously occupied by the hemodialysiscatheter, the PTA catheter comprising an elongated shaft having aninfusion lumen, an expandable dilatation chamber disposed on theelongated shaft, and one or more infusion openings in communication withthe infusion lumen positioned proximally adjacent to the expandabledilatation chamber, expanding at least the expandable dilatation chamberto disrupt fibrin sheath material present along the vascular accesspath, administering a radiographic contrast enhancing agent through theone or more infusion openings, and radiographically imaging the vascularaccess path and associated fibrin sheath material. The expandabledilatation chamber comprises an inflatable balloon. The method maycomprise expanding and contracting the dilatation chamber multiple timeswhile radiographically imaging the vascular access path and the fibrinsheath material. The method may comprise radiographically imaging atleast a portion of the jugular vein. Expanding the expandable dilatationchamber may comprise expanding an expandable rigid spacer. The cathetermay include a single infusion opening.

In another implementation, a method of visualizing and/or treating acatheterization path for an implanted hemodialysis catheter, comprisesselecting a hemodialysis patient in need of an implanted hemodialysiscatheter, inserting a percutaneous transluminal angioplasty (PTA)catheter into the jugular vein or subclavian vein and then into thebrachiocephalic vein, the PTA catheter comprising an elongated shafthaving an infusion lumen, an expandable dilatation chamber disposed onthe elongated shaft, and one or more infusion openings in communicationwith the infusion lumen positioned proximally adjacent to the expandabledilatation chamber, expanding at least the expandable dilatation chamberto open a stenosis in the brachiocephalic vein, administering aradiographic contrast enhancing agent through the one or more infusionopenings, and radiographically imaging portions of the jugular veinand/or subclavian vein. The expandable dilatation chamber may comprisean inflatable balloon. Expanding the expandable dilatation chamber maycomprise expanding an expandable rigid spacer. The catheter may includea single infusion opening. The method may comprise expanding thedilatation chamber at one or more other stenoses in the venouscatheterization path.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced.

In the drawings:

FIGS. 1A-C schematically illustrate side cut views of exemplary narrowedsegments adjacent dialysis vascular access, in accordance with anembodiment of the present invention;

FIGS. 2A-D schematically illustrate side views of exemplary dilatationballoon catheters, in accordance with an embodiment of the presentinvention;

FIGS. 3A-B schematically illustrate side cut views showing distalportions of exemplary occlusion balloon catheters comprising exemplaryexpandable spacers, in accordance with some embodiments of the presentinvention;

FIGS. 4A-D schematically illustrate side views of an exemplarydilatation balloon catheter representing different stages in dilating anarrowed segment adjacent hemodialysis vascular access and occludingsame segment during material perfusions, in accordance with someembodiments of the present invention;

FIG. 5 schematically illustrate top cut views of an exemplary ballooncatheter deployed to occlude an anastomosed portion between a conduitand a graft while dispersing a fluid along graft length, in accordancewith some embodiments of the present invention;

FIGS. 6A-B schematically illustrate cross sectional cut views of twodilatation balloon catheters, in accordance with some embodiments of thepresent invention;

FIGS. 7A-D schematically illustrate different illnesses in vascularaccesses treatable by exemplary balloon catheters, in accordance withsome embodiments of the present invention;

FIGS. 8A-D schematically illustrate an exemplary balloon catheter havinga uniform diameter and cross sections thereof at different locationstherealong, in accordance with some embodiments of the presentinvention;

FIGS. 9A-C schematically illustrate an exemplary balloon cathetercomprising a combined infusion-guidewire lumen, in accordance withembodiments of the present invention;

FIGS. 10A-C schematically illustrate stages in a method for dilating anarrowed brachiocephalic vein portion and improving visualization in aninternal jugular vein, in accordance with some embodiments of thepresent invention; and

FIGS. 11A-F schematically illustrate stages in a method for fibrinsheath disruption, in accordance with some embodiments of the presentinvention.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The following preferred embodiments may be described in the context ofexemplary dilatation and/or recanalization systems and methods in bloodvessels, such as dialysis vascular access recanalization or treatmentprocedures, for ease of description and understanding. However, theinvention is not limited to the specifically described devices andmethods, and may be adapted to various clinical applications withoutdeparting from the overall scope of the invention.

The present invention, in some embodiments thereof, relates to systemsand methods for treating narrowed or occluded blood vessels, and inparticular to dilatation balloon catheters for dilating occluded ornarrowed vein, artery or graft portions such as in dialysis vascularaccess or at remote locations. In some embodiments of the invention, thedilatation balloon catheters of the present invention are capable and/orconfigured to exert and maintain enough dilatation pressures such asmoderate-to-high pressures over 1 atmospheres or more, optionally 5atmospheres or more, or ultra-high pressures of 15 atmospheres or more,optionally 25 atmospheres or more. In some embodiments, the dilatationballoon catheters of the present invention are capable and/or configuredto remain inflated, optionally at least partly when inflated to chosenpressures, for prolonged continuous periods, optionally 1 minute ormore, optionally 3 minutes or more, optionally 10 minutes or more.

In some embodiments of the present invention, at least part of the timewhile remaining inflated, the balloon catheter is used to disperse afluid, optionally continuously, into the vascular access (e.g., graft orfistula), optionally an infusion material containing at least one of acontrast enhancing agent, a drug agent (e.g., antimitotic agent) and aflushing fluid (e.g., saline). Optionally, the dilatation balloon atleast partly occludes the target blood vessel or graft (e.g., a vascularaccess) during at least part of the infusion period, thereby loweringthe blood flow rate therethrough or completely stops it. Optionally, theinfusion material is dispersed via an infusion port provided proximallyto, optionally adjacent, the balloon.

Referring now to the drawings, FIGS. 1A-C schematically illustrate sidecut views of exemplary narrowed segments adjacent dialysis vascularaccess, in accordance with an embodiment of the present invention. FIG.1A shows a narrowing NR1 at a junction of vein V and an arteriovenous(AV) graft AVG interconnecting vein V and an artery A. FIG. 1B shows anarrowing NR2 located in vein V adjacent its junction with graft AVG.FIG. 1C shows an obstruction or a complete narrowing NR3 located in anarteriovenous fistula AVF adjacent junction of vein V and artery A. Suchnarrowing or obstructions may be formed of any combination of differentfactors commonly resulting change of natural blood flow regimes,artifact anastomoses and/or introduction of PTFE or other synthetic ornatural grafts.

Dr. Prabir Roy-Chaudhury in “Hemodialysis Vascular AccessDysfunction—Opportunities for Targeting an Unmet Clinical Need” (USRenal Disease, 2006), the disclosure of which is fully incorporatedherein by reference, lists several factors. In early fistula failure,often evidenced as a stenotic venous and/or arterial segment very closeto the junction, the failure to reach mature fistulas is believed toinclude a multifactorial etiology as a result of diverse insultsincluding: (a) hemodynamic stressors that predispose to endothelialdamage and constriction rather than dilation; (b) vascular injury at thetime of surgery, especially as a result of venous tension and/or torque;(c) poor venous and arterial anatomy (vessel size and configuration);(d) previous venipunctures; (e) demographic factors such as race,gender, ethnicity and obesity; and (f) genetic factors that influencethe aggressiveness of the response to injury cascade. Late fistulafailure and AV graft stenosis begins from venous neointimal hyperplasia(VNH), which results in venous stenosis followed by thrombosis. In thesetting of AV grafts this occurs most commonly at the graft-veinanastomosis or in the first 2-3 cm of proximal vein, although stenosiswas evidenced at any different points within the entire dialysis accesscircuit. Alternative mechanisms for vascular stenosis include: vascularremodeling, adventitial migration from the adventitia into the intimaand presence of circulating stem cells.

An aspect of some embodiments of the present invention relates to adilatation balloon catheter comprising an expandable chamber sized andconfigured to expand a vein lumen portion above a nominal size thereof.Such a balloon may be referred to as an “angioplasty balloon.” The veinmay be a cephalic vein or a basilic vein. Optionally, the vein is abrachiocephalic vein. The nominal size of the vein lumen portion may beat least 3 mm, optionally at least 6 mm, optionally at least 10 mm, orhigher, but it will be appreciated that lumen sizes lower than thesevalues, or at any intermediate value can be treated with the methods anddevices described herein. In some embodiments of the invention, theexpandable chamber is capable of opening a narrowed and/or obstructedsegment and/or recanalizing vessel such as a dialysis vascular access.The vascular access may be an arteriovenous graft or an arteriovenousfistula.

In some embodiments of the invention, the expandable chamber comprisesan inflatable balloon. In some embodiments, the inflatable balloon isdesigned for burst pressures exceeding 1 atmosphere, optionallyexceeding 5 atmospheres. In some embodiments, the balloon is a highpressure balloon configured to maintain a non-ruptured form underinflation pressures exceeding 15 atmospheres, optionally exceeding 20atmospheres, optionally exceeding 30 atmospheres, or higher. Inexemplary embodiments, the inflatable balloon is configured to maintainsaid non-ruptured form under continuous and/or repeated expansions undersaid inflation pressures for at least 1 minute, optionally for at least3 minutes, optionally for at least 5 min, optionally for at least 10minutes, optionally for at least 30 minutes, or higher. Such prolongeddurations allow the use of the balloon to occlude, fully or partially, ablood vessel portion, optionally following dilatation of the portion oranother portion of the blood vessel, while optionally infusing a fluid(e.g., a contrast medium and/or a medicament) proximally to the balloon.Thus, in some advantageous embodiments, an angioplasty balloon may alsobe used as an occlusion balloon.

The dilatation balloon catheter includes an inflation lumeninterconnecting an inflation inlet port provided at its proximal end andan inflation exit port opened at the space created between the balloonwall and the catheter body segment enclosed by the balloon. In someembodiments, the balloon is inflated using saline, optionally withcontrast enhancing material.

In some embodiments, the dilatation balloon catheter further includes aninfusion exit port located proximally to the balloon or the expandablechamber for allowing an infusion material to exit the dilatation ballooncatheter. In some embodiments, the dilatation balloon catheter comprisesan infusion inlet port and an infusion lumen, intercommunicating theinfusion inlet port and the infusion exit port.

The infusion inlet port may be connectable to communicate with aninterior of an appendix reservoir containing infusion material. In afirst exemplary embodiment, the infusion material includes contrastenhancing fluid. In a second exemplary embodiments, the infusionmaterial comprising a medication that includes at least one activeagent, for example at least one of a mitotic inhibitor, a antimitoticagent, a mitosis modulator, an antineoplastic agent, anantiproliferative agent, an immunosuppressive agent, paclitaxel,sirolimus, zotarolimus, everolimus, Biolimus A9, an anticoagulationagent and heparin. In a third exemplary embodiment, the infusionmaterial comprising a medication solvent, enhancer and/or facilitator,for example a material, compound or agent that includes at least one ofan antiproleferative agent solvent, Cremophor EL, castor oil, ethanol,albumin, protamine sulfate, an antiproliferative agent enhancer,antibiotics and vitamin.

The infusion inlet port may be, optionally, alternatively oradditionally, connectable to a source for continuously flowable flushingfluid. Saline, with or without a contrast enhancing fluid, with orwithout medication, or any additive or enhancer of some sort, may beinjected to flush any residual clot material from the vessel.

Optionally, alternatively or additionally, the dilatation ballooncatheter further comprises a dedicated medication dispersion lumen forallowing a medication to pass therethrough and exit through a medicationexit port, which may be located adjacent to the infusion exit port,optionally distally, optionally proximally, optionally juxtaposing oroptionally circumferentially distant thereto.

In some embodiments of the invention, the dilatation balloon cathetercomprises a guidewire lumen for allowing a guidewire to passtherethrough and exit through a guidewire exit port located distally tothe infusion exit port. In some embodiments, the guidewire exit port islocated at the balloon catheter tip, distal to the balloon. Optionally,the infusion lumen is also a guide wire lumen so it is configured suchthat both a guidewire and infusion fluids are passable therethroughaccording to need. In some embodiments, such a multifunctional lumenincludes at least one inlet port or optionally two inlet ports forinsertion of fluids and guidewire, and at least two exit ports—aproximal exit port provided proximally to balloon for dispersion ofinfusion fluids, and a distal exit port provided distal to the balloon,meant for guidewire passage. Optionally, fluids are injected only whenguidewire is absent or alternatively when guidewire is at leastpartially enclosed in the infusion lumen. Optionally at least onevalving mechanism is provided in the infusion lumen so that fluids areselectively set to disperse only from the proximal exit port and notfrom the distal exit port. Balloon catheters comprising a combinedinfusion-guidewire lumen, a proximal infusion exit port and valvingmechanism are described in U.S. Provisional Application No. 61/752,649,the disclosure of which is fully incorporated herein by reference.

Reference is now made to FIGS. 2A-D which schematically illustrate sideviews of exemplary dilatation balloon catheters 100, 150, 200 and 250,respectively, in accordance with an embodiment of the present invention.

In FIG. 2A, dilatation balloon catheter 100 includes an elongate shaft110 connectable at its distal end with a balloon 120. Shaft 110 may bemade from a biocompatible polymer, rigid or semi-rigid, as known to art.Balloon 120 may be an occlusion balloon type and/or a dilatation balloontype; and may include a compliant, a semi-compliant, a non-compliant, oran ultra-non-compliant wall (for example, comprising a non-compliantpolymeric layer impregnated with non-stretchable strengthening fibers,such as Kevlar). In many advantageous embodiments, balloon 120 isconfigured so that it can function effectively as both a dilatationballoon and an occlusion balloon. In some cases, as described above,this may be accomplished by having the balloon material and inflationproperties satisfy a Shaft 110 includes an inflation lumen 126 providedalong a length thereof, interconnecting an inlet inflation port 128,located at a proximal end thereof, and an inflation exit port 124provided at balloon 120 interior 122. Balloon 120 may be inflatable bypressurizing inflation medium to its interior through inflation exitport 124. Inflation medium may include saline or oil, with or withoutcontrast enhancing materials.

Shaft 110 also includes infusion means 130 including an infusion lumen134 interconnecting an infusion inlet port 136, located at a proximalend thereof, and an infusion exit port 132 located distally to infusioninlet port 136 but proximal and adjacent to balloon 120. The advantageof positioning the infusion exit port proximally to the balloon, in casethat the balloon serves to occlude unwanted directional passage, is thatthe infusion material may be directed proximally to the balloon therebyimproving efficiency and safety of the procedure, optionally allowingvisualization and/or preventing clot formation in the conduit. Afterproperly occluding the vein portion, contrast material and/orthrombolytic drugs may be safely injected prior to restoration of flowthereby preventing concerns relating to the migration of clots into thearterial system. In some embodiments (not shown), infusion lumen 134 isopened at more than one infusion exit ports located adjacent or proximalto infusion exit port 132 but in any event proximal to balloon 120.Optionally and alternatively (not shown), infusion exit port 132 ispositioned distally to balloon 120 thereby allowing flow of infusionmaterial only distally and away from balloon 120.

Dilatation balloon catheter 100 includes a guidewire 140 provided inguidewire lumen 144 extending in and along shaft 110 and interconnectingproximal guidewire entry 146 and distal guidewire opening 142.Dilatation balloon catheter 110 may be an over-the-wire (OTW) typecatheter or a rapid-exchange (Rx) type catheter.

In some embodiments of the invention, dilatation balloon catheter 100may be used for percutaneous transluminal angioplasty (PTA), for examplefor dilating and/or recanalizing narrowed portion NR1 shown in FIG. 1A,narrowed portion NR2 shown in FIG. 1B and/or obstructed or fullynarrowed portion NR3 shown in FIG. 1C. Optionally, balloon 120 isinflatable to high pressures capable of opening narrowing in stenoticcephalic or basilica veins, optionally to 15 atmospheres or higher,optionally to 20 atmospheres or higher. Optionally and additionally,balloon 120 may be pressurized to at least partially take the form of anentire cross section along a lumen section to thereby occlude the lumensection and prevent flow of infusion material to pass therethrough. Insome embodiments, balloon 120 includes a compliant or a semi-compliantportion and in same or other embodiments, balloon 120 includes anon-compliant or an ultra-non-compliant portion.

In some embodiments, a dilatation balloon catheter according to aspectsof the present invention includes an expandable chamber which comprisesa compliant layer expandable to take a form constrained by surroundingboundaries of the vein lumen portion, optionally readily expanded abovesaid nominal size, and to occlude the lumen portion from a contrastenhancing fluid passing between periphery thereof and the surroundingboundaries. Optionally, additionally or alternatively, the expandablechamber comprises a non-compliant layer expandable to form the veinlumen portion to an expanded size above a nominal size having predefinedboundaries.

In some embodiments of the invention, the dilatation balloon catheterincludes a first independently inflatable balloon having a compliantlayer and a second independently inflatable balloon having anon-compliant layer. Optionally, the expandable chamber comprises thesecond independently inflatable balloon and is positioned proximallydistanced to the first independently inflatable balloon. Optionally andalternatively, the expandable chamber comprises the second independentlyinflatable balloon and is disposed within the first independentlyinflatable balloon.

In FIG. 2B, dilatation balloon catheter 150 includes a similar design ofcatheter 100 comprising elongated shaft 110, dilatation balloon 120provided at distal end thereof and communicating with inflation inletport 128, and guidewire 140 provided along a dedicated lumen extendingpartially along shaft 110 length. Vein occlusion means 160 is providedseparately to dilatation balloon 120 and comprising an occlusion balloon162 positioned adjacently proximally to dilatation balloon 120.Occlusion balloon 162 is inflatable by introduction of inflation medium(e.g., saline) through an inflation exit lumen 164 communicating withits interior. Inflation exit port 164 is interconnected via an inflationlumen 166 to an inflation inlet port 168 located at a proximal end ofshaft 110. An infusion exit port 172 is provided adjacent and proximalto occlusion balloon 162 and is interconnected via an infusion lumen 174to an infusion inlet port 176 located at the proximal end of shaft 110.

In some embodiments, balloon 120 includes a non-compliant or anultra-non-compliant layer and is capable of being inflated withoutrupture or yielding under pressures exceeding 15 atmospheres. Suchpressures may be maintained or be occasionally repeated for prolongeddurations, for example of 1 minute or more, or even up to 30 minutes oreven more than 30 minutes, in which prolonged dilatations are made forimproved yielding and reforming of the narrowed vein segment to anexpanded form and/or infusion material (e.g., contrast media, flushingfluid and/or medication) is continuously injected in directionallyallowed path in the vein and/or vascular access lumen for improvedefficacy. In some embodiments, occlusion balloon 162 includes acompliant or a semi-compliant layer and is designed for inflationpressures of less than 15 atmospheres, optionally less than 10atmospheres, optionally less than 5 atmospheres, optionally about 1atmosphere or less. In some embodiments, dilatation balloon 120 isconfigured to maintain high pressures for 1 to 3 minutes periods, orhigher, or lower, whereas occlusion balloon 162 is configured tomaintain lower pressures for 1 to 30 minutes, or higher, or lower.

In FIG. 2C, dilatation balloon catheter 200 includes a similar design ofcatheters 100 or 150, comprising elongated shaft 110, dilatation balloon120 provided at distal end thereof and communicating with inflationinlet port 128, and guidewire 140 provided along a dedicated lumenextending partially along shaft 110 length. Vein occlusion means 210 isprovided over dilatation balloon 120 and comprising an occlusion balloon212 sized and positioned to enclose or encapsulate dilatation balloon120. Occlusion balloon 212 is inflatable by introduction of inflationmedium (e.g., saline) through an inflation exit lumen 214 communicatingwith its interior. Inflation exit port 214 is interconnected via aninflation lumen 216 to an inflation inlet port 218 located at a proximalend of shaft 110. Infusion exit port 172 is now provided adjacent andproximal to occlusion balloon 212 on shaft 110.

In some embodiments, dilatation balloon 120 includes a non-compliant oran ultra-non-compliant layer and is capable of being inflated withoutrupture or yielding under pressures exceeding 15 atmospheres. In someembodiments, occlusion balloon 212 includes a compliant or asemi-compliant layer and is designed for inflation pressures of lessthan 15 atmospheres, optionally less than 10 atmospheres, optionallyless than 5 atmospheres, optionally about 1 atmosphere or less. In someembodiments, dilatation balloon 120 is configured to maintain highpressures for 1 to 3 minutes periods, or higher, or lower, whereasocclusion balloon 212 is configured to maintain lower pressures for 1 to30 minutes, or higher, or lower. In some embodiments, dilatation balloon120 is configured to inflate at high pressures when the coveringocclusion balloon 212 is deflated, though compliant enough to take theform of the inflated dilatation balloon 120. In some embodiments,occlusion balloon 212 is configured to inflate to occlude and take aform of a vein lumen portion when dilatation balloon 120 is deflatedand/or at least partially inflated.

In FIG. 2D, dilatation balloon catheter 250 includes a similar design ofcatheter 100, comprising elongated shaft 110, dilatation balloon 120provided at distal end thereof and communicating with inflation inletport 128, and guidewire 140 provided along a dedicated lumen extendingpartially along shaft 110 length. A separate medication dispersion exitport 262 is provided adjacent infusion exit port 132 adjacent andproximal to balloon 120. Medication dispersion exit port 262 isinterconnected via a medication dispersion lumen 264 to a medicationinlet port 266 located at a proximal end of shaft 110. This way,medication may be dispersed in vein lumen while other infusion materialsare injected or withheld, according to need, via infusion exit port 132.In sequence or in parallel, or in any combination thereof, contrastmedia, medication, other active agents, active agent enhancers orfacilitators, flushing fluids, or other flowable materials, may bedispersed via exit ports 132 and/or 262.

In some embodiments of the present invention, a dilatation ballooncatheter is coated or impregnated, at least partially, with at least oneof mitotic inhibitor, antimitotic agent, mitosis modulator,antineoplastic agent, antiproliferative agent, immunosuppressive agent,paclitaxel, sirolimus, zotarolimus, everolimus, Biolimus A9,anticoagulation agent, and heparin.

In some embodiments, additionally or alternatively to previous shownembodiments, the expandable chamber comprises an expandable rigidspacer, wherein a compliant layer is disposed between the spacer and thesurrounding boundaries. In some embodiments, the spacer comprises aself-expandable member provided in covering sheath. Optionally, theself-expandable member is radially expandable when the covering sheathis proximally withdrawn. Optionally and alternatively, the spacercomprises a selectively expandable cage member. Optionally andalternatively, the spacer comprises a braid selectively compressiblefrom a first length indicative of a smaller spacer diameter to a secondlength indicative of a greater spacer diameter. Optionally,alternatively or additionally, the spacer comprises a shape memorymaterial and is shapeable from a first slender shape at less than bodytemperature to a second expanded shape at body temperature.

Reference is now made to FIGS. 3A-B which schematically illustrate sidecut views showing distal portions of exemplary occlusion ballooncatheters 300 and 400, respectively, comprising exemplary expandablespacers, 330 and 430, respectively, in accordance with some embodimentsof the present invention.

In FIG. 3A, occlusion balloon catheter 300 includes a balloon 310 havinga compliant layer 312 enclosing an interior 314. In some embodiments,balloon 310 is a drug eluting balloon (DEB), coated with drug layer 340,and is especially fitted and configured to treat and/or prevent, atleast partially, stenosis and/or restenosis in veins, optionallyspecifically in cephalic and/or basilic veins. In some embodiments, druglayer 340 includes an antiproliferative agent, such as a solid form orpowdered paclitaxel. Occlusion balloon catheter 300 includes a hollowshaft 320 comprising a rigid, semi-rigid or elastic wall 322 enclosingan inflation lumen 328 and a spacer actuation lumen 329. Hollow shaft320 at its distal end is protruding in interior 314 of balloon 310 suchthat inflation exit port 326 and spacer actuation opening 324 is fixedlypositioned therein. A self-expandable spacer 330 is selectivelydeployable to self-expand in interior 314 or extractable to a smallercollapsed form when pulled into spacer actuation lumen 329. Shown inFIG. 3A an intermediate stage where a distal portion 332 ofself-expandable spacer 330 is protruding out of lumen 329 throughopening 324 to expand in interior 314, while a proximal portion 334 iskept in collapsed form in lumen 329. Relative positioning ofself-expandable spacer 330 in spacer actuation lumen 329 is applicablewith rod 336 connected to proximal end of spacer 330 and is configuredto push or pull spacer 330 in lumen 329 as appropriate.

In some embodiments, balloon 310 is a compliant balloon sized andconfigured to allow occlusion of a lumen in a cephalic or a basilic veinportion while infusion material and/or medication and/or flushing mediumis dispersed in the vein lumen, while preventing flowing of suchmaterials distally across balloon 310. In some embodiments, balloon 310is not configured to inflate at high pressures to apply PTA expansiveforces, thus incapable of dilating a narrowed or an obstructed veinportion, adjacent a hemodialysis vascular access. Such dilatation isapplicable by releasing self-expandable spacer 330, at least partially,to an expanded form being equal or greater than a nominal size of veinlumen. In some embodiments, when expanding, spacer 330 exerts forceshaving magnitudes high enough to dilate the narrowed or obstructedportion. Self-expandable spacer 330 may be kept continuously released asneeded, for example for periods of 1 minute or more, and may beextracted or released as needed.

In FIG. 3B, occlusion balloon catheter 400 includes a balloon 410 havinga compliant layer 412 enclosing an interior 414. In some embodiments,balloon 410 is especially fitted and configured for PTA procedures incephalic and/or basilic veins. Occlusion balloon catheter 400 includes ahollow shaft 420 comprising a rigid, semi-rigid or elastic wall 422enclosing an inflation lumen 428 and a spacer actuation lumen 429.Hollow shaft 420 at its distal end is protruding in interior 414 ofballoon 410 such that inflation exit port 426 and spacer actuationopening 424 is fixedly positioned therein. A selectively expandable cage430 is selectively deployable to expand or contract, as chosen, ininterior 414. Shown in FIG. 3B fully deployed stage where cage 430 isfully expanded. Cage 430 comprises a core member 432, a plurality ofpressing members 436 that are hingedly connected to actuation members438 interconnecting them to core member 432. Actuation of cage 430 isapplicable with rod 434 connected to proximal end of core member 432. Ajackscrew mechanism (not shown) is embedded in core member 432 such thatclockwise rotation of rod 434 will force cage 430 to expand up to itsmaximal expanded size, whereas a counterclockwise rotation of rod 434will collapse cage 430 up to a fully collapsed form (not shown).

In some embodiments, balloon 410 is a compliant balloon sized andconfigured to allow occlusion of a lumen in a cephalic or a basilic veinportion while infusion material and/or medication and/or flushing mediumis dispersed in the vein lumen, while preventing flowing of suchmaterials distally across balloon 410. In some embodiments, balloon 410is not configured to inflate at high pressures to apply PTA expansiveforces, thus incapable of dilating a narrowed or an obstructed veinportion, adjacent a hemodialysis vascular access. Such dilatation isapplicable by forcing cage 430 to expand, selectively, to a chosen size,being equal or greater than a nominal size of vein lumen. In someembodiments, when expanding, cage 430 exerts forces having magnitudeshigh enough to dilate the narrowed or obstructed portion. Cage 430 maybe kept continuously expanded as needed, for example for periods of 1minute or more, and may be collapsed and expanded as needed. If a drugcoated balloon or drug impregnated balloon in dialysis access needs tobe inflated for prolonged periods to time to reach better effectivenessthe proximal infusion port can be used for intermittent or confusioninfusion of fluid to prevent clot formation during the prolongedtreatment.

Also, if a mode of drug delivery to the stenosed segment includesinfusion of the drug directly into the stenosed segment through a porousor fenestrated balloon and the drug being infused over a prolongedperiod of time into the diseased segment, then the proximal infusionport can be used to maintain access patency during the procedure.

In an aspect of some other embodiments of the present invention, thereis provided a method for recanalizing a hemodialysis vascular access,optionally in a narrowed, obstructed or otherwise stenotic portion in abasilica or cephalic vein portion. In some embodiments, the methodcomprising at least one of the following steps, not specifically in suchorder:

inserting a dilatation balloon catheter in a narrowed vein lumen portionadjacent a dialysis vascular access through an opening in the dialysisvascular access;

positioning the expandable chamber appositionally to the lumen portion;

expanding the expandable chamber to expand the lumen portion to aboveits nominal size;

applying the dilatation balloon catheter to occlude the expanded lumenportion; and

administering contrast enhancing fluid through the infusion exit port.

In some embodiments, the step of applying the dilatation balloon toocclude the lumen portion is comprised in the step of expanding theexpandable chamber to expand the lumen portion. Optionally, suchapplying and/or expanding comprises inflating a first independentlyinflatable balloon. Optionally, such inflating includes elevating apressure in the first independently inflatable balloon to a maximalpressure being at least 15 atmospheres. Optionally, such a maximalpressure is maintained and/or repeatedly obtained for at least 1 minute.Optionally and alternatively, after a dilatation of a narrowed vesselportion, the balloon is used to occlude same or other vessel portion insubstantially lower pressures as were applied during the dilatation. Insome embodiments, the first independently inflatable balloon is coatedor impregnated with a first anti-restenosis medication.

Optionally and alternatively, the applying comprises expanding anexpandable rigid spacer.

Optionally, alternatively or additionally, the method further includesthe step of delivering a second anti-restenosis medication through theinfusion exit port.

In some embodiments, the first anti-restenosis medication and/or thesecond anti-restenosis medication comprises at least one of a mitoticinhibitor, an antimitotic agent, a mitosis modulator, an antineoplasticagent, an antiproliferative agent, an immunosuppressive agent,paclitaxel, sirolimus, zotarolimus, everolimus, Biolimus A9, ananticoagulation agent, and heparin.

In some embodiments, the method further includes the step of flushingthe narrowed vein lumen portion with a continuous stream of flushingfluid through said infusion exit port.

Reference is now made to FIGS. 4A-D which schematically illustrate sideviews of dilatation balloon catheter 100 representing different stagesin dilating a narrowed segment NR of vein V adjacent hemodialysisvascular access and occluding same segment during material perfusions,in accordance with some embodiments of the present invention. As shownin FIG. 4A, catheter 100 is provided towards narrowed segment NR overguidewire 140 until balloon 120 is nested therein. As chosen, and asshown in FIG. 4B, balloon 120 is inflated to dilate narrowed segment NRto over its nominal size. Balloon 120 is optionally a high pressureand/or non-compliant balloon, optionally strengthened with reinforcingfibers, such as aramid or para-aramid synthetic fibers (e.g., Kevlar™,made by Du-Pont™), although other fibers or wires types (e.g., dyneema,twaron, nylon, vectran or others) or other strengthening means ordesigns (e.g., wall thickening) may be used. Balloon 120 may bemaintained in a chosen expanded shape for prolonged periods, for example1 minute or more, optionally 3 minutes or more, optionally 5 minutes ormore, optionally 10 minutes or more.

In some embodiments, balloon 120 is configured to occlude, at leastpartly, the now expanded narrowed segment NR for travel of fluidstherethough. As shown in FIG. 4C, contrast medium 510 is then injectedvia infusion exit port 132 and is allowed to travel in vein V lumen onlyproximally and away from balloon 120. Medication 520 or any enhancers orfacilitators for medication may then be dispersed (as shown in FIG. 4D)via infusion exit port 132 and, based on its physical properties (e.g.,viscosity and/or relative specific gravity) may be kept adjacentnarrowed segment NR for prolonged periods, optionally over 5 minutes,optionally over 10 minutes.

Reference is now made to FIG. 5 which schematically illustrate top cutviews of balloon catheter 100 when deployed to occlude an anastomosedportion between a conduit C1 and a graft AVG, connecting conduit C1 anda conduit C2, while dispersing a fluid along graft AVG length, inaccordance with some embodiments of the present invention. In a firstembodiment, conduit C1 is a vein and conduit C2 is an artery. In someembodiments, balloon 120 is shown inflated following a dilatationprocedure to expand a local narrowing, in which it was dilated tomaximal pressures of 15 atmospheres or more, optionally 25 atmospheresor more. Optionally and alternatively, balloon 120 was not usedpreviously to dilate a narrowed portion. As shown, balloon 120 is shownexpanded to decrease or totally stop the blood flow rate therethroughtraveling upstream from conduit C2 (e.g., artery) to conduit C1 (e.g.,vein). In some embodiments, balloon 120 is kept inflated for at least 3minutes, optionally at least 10 minutes, optionally at least 20 minutesor even more. During inflation time, infusion material is dispersedthrough infusion exit port 132. Optionally, alternatively oradditionally, same or other infusion material is dispersed via afenestrated wall portion in balloon 120 (not shown). Dispersion materialmay include contrast medium 510 and/or medication 520. In this example,contrast medium 510 and/or medication 520 travels along graft AVG lengthin a reversed direction to that of a normal blood flow passing in thegraft in order to allow visualization and/or treat the graft and/oranastomosis areas. Optionally, alternatively or additionally, same orother medication than medication 520 is coating balloon 120 exterior. Insome embodiments, balloon 120 is gradually unpressured from ultra highpressures during infusion period, optionally until reaching 5atmospheres or less, optionally 1 atmosphere or less.

In some embodiments, same or similar treatment can be performed in afistula at an arteriovenous anastomosis area.

Optionally and alternatively, conduit C1 is an artery and conduit C2 isa vein, and balloon 120 is shown occluding, fully or partially, anarterial anastomosis area for treating most of all of graft AVG withmedication 520. In this example, balloon 120 is not or is not used fordilatation in order to avoid mechanical damage to the arterialanastomosis and adjacent tissues.

Optionally, alternatively or additionally, balloon 120 is repeatedlyused to dilate graft AVG at different portions along its length, while,optionally, medication 520 is dispersed, continuously or in between eachdilatations.

In some embodiments, balloon 120 is introduced into graft AVG andtravels therein until deployment when in a compressed form, in which itsouter diameter is same or smaller than outer diameter of shaft 110.

Reference is now made to FIGS. 6A-B which schematically illustrate crosssectional cut views of two dilatation balloon catheters, 100A and 100B,respectively, in accordance with some embodiments of the presentinvention. Catheter 100A is shown with a shaft 110A having a smallguidewire lumen 540A and two large inflation lumen 530A and infusionlumen 550A and catheter 100B is shown with a shaft 110B having a largeinflation lumen 530B and two small guidewire lumen 540B and infusionlumen 550B. Guidewire lumens 540A and 540B are of standard size allowingpassing therethrough of commercially available guidewires, such as thosehaving diameters between 0.015 and 0.025 inch. A large inflation lumen,as in lumens 530A and 530B, is needed for rapid inflation and deflationof balloon 120 being formed and configured to maintain a non-rupturedform under pressures exceeding 25 atmospheres or more during prolongedperiods of 1 minute or more. A large infusion lumen, such as lumen 550A,is needed in case of viscous contrast medium or medication and/or whenhigh flow rates are needed, for example for flushing. In someembodiments large lumens 530A, 550A and/or 530B are 0.03 inch or more indiameter, optionally 0.05 inch or more, optionally 0.1 inch or more,optionally 0.5 inch or more. In some embodiments of the invention,infusion lumens 550A and/or 550B respectively communicates with infusioninlet ports (not shown), each is further connectable to a source forcontinuously flowable flushing fluid.

Reference is made to FIGS. 7A-D which schematically illustrate differentillnesses in vascular accesses treatable by exemplary balloon catheters,in accordance with some embodiments. In FIG. 7A, a fistula type vascularaccess is shown in which a vein is connected to an artery at anarteriovenous anastomosis AVA. A narrowing NR is present in vein portionadjacent anastomosis AVA. Passage 610 shows introduction and travelroute of an exemplary balloon catheter according to the presentinvention (for example, balloon catheter 100) for treating narrowing NRand recanalizing the shown vascular access. In some embodiments, ballooncatheter 100 is used to perform angioplasty procedure with someadvantages originating from aspects of the present invention. Optionallyballoon 120 is non-compliant. The procedure includes at least one of thefollowing steps (not necessarily in same order):

-   -   1. Inserting balloon catheter 100 into the vein, optionally        through a vascular sheath, optionally over a guide wire (not        shown) and advancing it towards anastomosis AVA, generally along        passage 610, optionally guided under fluoroscopy, until reaching        narrowing NR;    -   2. performing angioplasty by dilating balloon 120 according to        need;    -   3. while the balloon is being inflated and/or is maintained        inflated (thereby optionally functioning as an occlusion        balloon), injecting contrast enhancing material via infusion        exit port 132 into the fistula, optionally allowing the contrast        media to flow towards the heart so that other possible narrowed        portions may be traced adjacent AVA or upstream;    -   4. deflating balloon 120 so blood can flow again through AVA        clearing the contrast enhancing material;    -   5. advancing balloon catheter 100, optionally approximately 4 to        5 cm beyond AVA into the artery, then injecting contrast        enhancing material once more to image the treated area of        anastomosis AVA and analyzing current condition and deciding if        further sessions are needed;    -   6. removing balloon catheter 100 and any other instrumentation        (such as guidewire and/or sheath).

In FIG. 7B, a fistula type vascular access is shown in which a vein isconnected to an artery at an arteriovenous anastomosis AVA. A narrowingNR is present in vein portion upstream and away from anastomosis AVA.Passage 620 shows introduction and travel route of an exemplary ballooncatheter according to the present invention (for example, ballooncatheter 100) for treating narrowing NR and recanalizing the shownvascular access. In some embodiments, balloon catheter 100 is used toperform angioplasty procedure with some advantages originating fromaspects of the present invention. Optionally balloon 120 isnon-compliant. The procedure includes at least one of the followingsteps (not necessarily in same order):

-   -   1. inserting balloon catheter 100 into the vein, optionally        through a vascular sheath, optionally over a guide wire (not        shown) and advancing it away from anastomosis AVA, generally        along passage 620, optionally guided under fluoroscopy, until        reaching a position proximal to or adjacent narrowing NR;    -   2. injecting contrast enhancing material via infusion exit port        132 in order to locater and/or observe narrowing NR;    -   3. advancing balloon catheter 100 further until reaching        narrowing NR;    -   4. performing angioplasty by dilating balloon 120 according to        need;    -   5. while the balloon is being inflated and/or is maintained        inflated (thereby optionally functioning as an occlusion        balloon), injecting contrast enhancing material via infusion        exit port 132 into the fistula, towards anastomosis AVA and into        the artery;    -   6. deflating balloon 120 so blood can flow again through AVA        clearing the contrast enhancing material;    -   7. injecting contrast enhancing material once more to image the        treated area, analyzing current condition and deciding if        further sessions are needed;    -   8. removing balloon catheter 100 and any other instrumentation        (such as guidewire and/or sheath).

In some embodiments, similar procedure can be performed to a narrowedgraft using some or all steps as described above.

In FIG. 7C, a fistula type vascular access is shown in which a vein isconnected to an artery at an arteriovenous anastomosis AVA. A narrowingNR is present in vein portion adjacent anastomosis AVA. Clottingsubstance CL is present in the vein and blocks flow passagetherethrough. Passage 630 shows introduction and travel route of anexemplary balloon catheter according to the present invention (forexample, balloon catheter 100) for clearing clotting substance CL andrecanalizing the shown vascular access. In some embodiments, ballooncatheter 100 is used to perform declotting procedure with someadvantages originating from aspects of the present invention. Optionallyballoon 120 is non-compliant. The procedure includes at least one of thefollowing steps (not necessarily in same order):

-   -   1. inserting balloon catheter 100 into the vein, optionally        through a vascular sheath, optionally over a guide wire (not        shown) and advancing it toward anastomosis AVA, generally along        passage 630, optionally guided under fluoroscopy, until reaching        anastomosis AVA;    -   2. inflating balloon 120 at junction in order to prevent clots        from entering the artery;    -   3. while the balloon is being inflated and/or is maintained        inflated (thereby optionally functioning as an occlusion        balloon), injecting contrast enhancing material via infusion        exit port 132 into the fistula;    -   4. imaging (taking angiogram) the vein to locate blocked and        narrowed areas (with clots CL and/or narrowing NR);    -   5. injecting clot dissolving material via an opening proximal to        balloon 120 (optionally via infusion exit port 132 or another        dedicated medicament exit port) until clots CL dissolve and        disengage from vein walls;    -   6. still while the balloon is being inflated and/or is        maintained inflated (thereby optionally functioning as an        occlusion balloon), injecting again contrast enhancing material        via infusion exit port 132 into the fistula;    -   7. deflating balloon 120 so blood can flow again through AVA        clearing dissolved clots CL and the contrast enhancing material;    -   8. removing balloon catheter 100 and any other instrumentation        (such as guidewire and/or sheath).

In FIG. 7D, a graft type vascular access is shown connecting a vein toan artery. Clotting substance CL is present in the graft and blocks flowpassage therethrough. Passages 640 and 650 show consecutive introductionand travel route of an exemplary balloon catheter according to thepresent invention (for example, balloon catheter 100 with a compliantocclusion type balloon) for clearing clotting substance CL andrecanalizing the shown vascular access. In some embodiments, ballooncatheter 100 is used to perform declotting procedure with someadvantages originating from aspects of the present invention. Theprocedure includes at least one of the following steps (not necessarilyin same order):

-   -   1. inserting an occlusion type balloon catheter 100 into the        vein or in graft AVG adjacent vein, optionally through a        vascular sheath, optionally over a guide wire (not shown) and        advancing it away from the venous anastomosis, generally along        passage 640, optionally guided under fluoroscopy, until reaching        the arterial anastomosis;    -   2. inflating balloon 120 in order to prevent clots from entering        the artery;    -   3. while the balloon is being inflated and/or is maintained        inflated, injecting contrast enhancing material via infusion        exit port 132 into graft AVG;    -   4. imaging (taking angiogram) graft AVG to locate blocked areas        (with clots CL);    -   5. injecting clot dissolving material via an opening proximal to        balloon 120 (optionally via infusion exit port 132 or another        dedicated medicament exit port) until clots CL dissolve and        disengage from vein walls;    -   6. pulling back the inflated balloon 120 to possibly dislodge an        arterial plug;    -   7. deflating balloon 120 and injecting contrast enhancing        material via infusion exit port 132 into the graft;    -   8. removing balloon catheter 100 and any other instrumentation        (such as guidewire and/or sheath);    -   9. optionally repeating at least one of steps 1-8 in an opposite        route, such as generally along passage 650.

In some embodiments, balloon catheters according to the presentinvention are deployed (inserted and progressed in the vasculature)without use of a sheath (a “sheathless procedure”).

In some embodiments, a balloon dilatation catheter according to thepresent invention includes three lumens passing at least partiallytherealong and has a substantially uniform diameter with the dilatationballoon outer diameter being substantially equal or smaller than theouter diameter of the catheter body, when it is the collapsed formation,for example during travel in the cardiovascular vessels and beforedeployment. In some embodiments, only the distal portion of the ballooncatheter, distally to the dilatation balloon, is substantially smallerin diameter, optionally including a single lumen, optionally a lumenintended for passing a guidewire therethrough. Optionally andadditionally, when the balloon collapses after deflation, it regainsouter diameter being equal or smaller than that of the catheter shaft.Maintaining such small dimension throughout balloon dilatation catheterlength allows the use of smaller introducer sheathes.

FIGS. 8A-D schematically illustrate an exemplary balloon catheter 1000having a uniform diameter, and cross sections thereof at differentlocations therealong. Balloon catheter 1000 may be similar or identicalto catheter 100 in at least one of size, balloon type and infusion portlocation, or may be a variation thereof. Catheter 1000 includes anelongated body 1100 having a length and at least three portions withdifferent cross sections and different outer diameters as shown in FIGS.8B-D. In its distal end, elongated body is covered, partially, with adilatation balloon 1200. In some embodiments, balloon 1200 is collapsedand maintained folded, optionally rolled, over a dedicated recessedportion of elongated body 1100. In an optional design (not shown), anouter sheath holds balloon 1200 tightly in its rolled/collapsedformation until inflation, optionally the outer sheath bursts and/ordiscarded, optionally in a dedicated cabinet in elongated body 1100.

In its proximal portion, being the longest, elongated body 1100 includesa cross section as shown in FIG. 8B, defining an infusion lumen 1310, aballoon inflation lumen 1320 and a guidewire lumen 1330. Infusion lumen1310 may be sized and configured such to allow medically approved flowrates of at least one of contrast enhancing flowable material, flowablemedication and/or flushing liquid (e.g., saline). Balloon inflationlumen 1320 may be sized and configured such to allow rapid andcontinuous inflation of dilatation balloon 1200. Guidewire lumen 1330may be sized and configured such to allow passing therethrough and/orriding over wires being 0.01 to 0.03 inch in diameter, optionally 0.015to 0.025 inch in diameter. All three lumens travel along the entirelength of the proximal segment and originating with the dedicated inletports, namely: infusion inlet port 1110, balloon inflation inlet port1120 and guidewire inlet port 1130. In this exemplary embodiment,guidewire lumen 1330 is relatively small and is located at the center ofthe proximal portion of catheter body 1100, while infusion lumen 1310and inflation lumen 1320 are substantially greater in size in order toallow high flow rates of both infusion and inflation media. Infusionlumen ends at the premises of an infusion exit port 1140.

Next to its distal end portion, elongated body 1100 is reduced in sizeto allow integration with balloon 1200 which gradually adds to its outerboundaries, when in collapsed form, an overall diameter beingsubstantially the same or slightly smaller than the outer diameter ofthe proximal portion of elongated body 1100. A 2^(nd) cross section ofelongated body 1100, illustrated 20 in FIG. 8C, shows its size reductionwhen reduced to two lumens, namely, guidewire lumen 1330 and ballooninflation lumen 1320. Balloon inflation lumen 1320 ends with inflationexit port 1150 positioned inside balloon 1200. A 3^(rd) cross section ofelongated body 1100, illustrated in FIG. 8D, shows a further reductionin diameter, now only slightly larger than guidewire lumen 1330. Still,balloon 1200 at its compacted/rolled state adds diameter to reach anoverall outer diameter substantially same or smaller than that ofelongated body 1100 at its proximal portion, as described above.Optionally, elongated body 1100 further extends distally away fromballoon 1200, so that catheter 1000 end portion is substantially smallerin diameter. At the distal tip of elongated body 1100, there is locatedan opening 1160 of guidewire lumen 1330 through which a guidewire (notshown) may outwardly extend.

In some occasions, minimization of catheter's lumens cross-sections isadvantageous. In one example, there may be a need for a small diametercatheter for intraluminal passage (e.g., 3 F to 5 F) so it is morecomplex to introduce three lumens. In a second example, there may be aneed to fortify the catheter shaft for high pressure dilatations (as invascular access recanalization in certain anatomies), so it may beadvantageous to decrease overall lumens size in a certain shaftdiameter. In some embodiments, a dilatation balloon catheter accordingto the present disclosure includes a single lumen which is used, atleast in part, both for fluids transfer and dispersion (“infusion”) aswell as for guidewire passage.

Reference is made to FIGS. 9A-C which schematically illustrate anexemplary dilatation balloon catheter 2000 comprising a combinedinfusion-guidewire lumen (referred to as infusion lumen 2114) with anoptional selective valving mechanism 1300. Catheter 2000 includes ashaft 2100 having, a length, a proximal end and a distal end, and a wallenclosing infusion lumen 2114 which is extending along shaft's 2100length and opened at both proximal and distal ends with correspondingproximal opening 2112 and distal opening 2118. Infusion lumen 2114 isfurther opened with a lateral infusion opening 2116 disposed in shaft's2100 wall between the proximal end and the distal end.

An inflatable member 2200 is connected to shaft 2100 adjacent its distalend, distal to lateral infusion opening 2116. An inflation lumen 2124,sealed to infusion lumen 2114, extends between a proximal inflationopening 2122, at shaft's 2100 proximal end, and a distal inflation port2126, opened to an interior of inflatable member 2200. Inflatable member2200 may be a compliant balloon, a semi-compliant balloon or anon-compliant balloon.

A valving mechanism according to the present disclosure may be any typeof controller, such as a mechanical device, for selectively controllinga flow parameter of a fluid, for example a flow rate. A valvingmechanism may be set between two or more modes, including a fully closedmode in which flow is substantially absent, and a fully opened valve inwhich fluid is allowed to travel in maximal velocity. According to somepreferred embodiments of the present disclosure, a valving mechanismincludes an elongated member such as a wire (e.g., a guide wire)operational to selectively pass through or withdraw from an infusionlumen portion sized and shaped substantially the same as externalboundaries of a correlating portion thereof, such that when uponoccupying the infusion lumen portion then substantially or completely noflow will pass therethrough, while when it is fully withdrawn from theinfusion lumen portion, fluid passage can be feasible. An optionalvalving mechanism may be provided in infusion lumen 2114 distal tolateral infusion opening 2116. Valving mechanism may be selectivelyoperable to block distal opening 2118 of infusion lumen 2114 such thatfluid passing distally through infusion lumen 2114 shall exit mainly orsolely through lateral infusion opening 2116 rather than through distalopening 2118. In case that the valving mechanism is set not block distalopening 2118, more flow may pass via distal opening 2118.

As shown, infusion lumen 2114 defines a first segment 2320, extendingbetween proximal opening 2112 and a boundary 2340 adjacent lateralinfusion opening 2116, and a second segment 2330, extending betweenboundary 2340 and distal opening 2118. In some embodiments, firstsegment 2320 has a first minimal cross section area and second segment2330 has a second minimal cross section area smaller than the firstminimal cross section of first segment 2320. Valving mechanism mayinclude an elongated member, preferably a guide wire 2310 selectivelydisposable in the first and second minimal cross sections. Guidewire2310 is preferably sized and configured to pass through proximal opening2112, infusion lumen 2114 and distal opening 2118, and therefore allowan over-the-wire delivery of catheter 1000 thereupon.

In some embodiments, the second minimal cross section is sized andshaped such that guide wire 2310 can be selectively fit, snugly, in thesecond minimal cross section in order to achieve blocking of distalopening 2118 and/or second segment 1330 distal to lateral infusionopening 2116. In some embodiments, the second minimal cross section iscircular whereas the first minimal cross section is sized and shaped tovirtually enclose a circle with identical dimensions to said secondminimal cross section (as shown in the shape difference of infusionlumen 2114 in FIG. 9B vs. FIG. 9C). The first minimal cross section maybe circular, elliptic or crescent shaped.

A dilatation balloon catheter, such as balloon catheters 100, 1000 or2000, can also be used to treat stenotic vein portions beingsubstantially remote from site of anastomosis and/or dialysis access, orat occasions where hemodialysis is absent. A common scenario, forexample when a vascular access is needed immediately or if AV fistulaeor AV shaft implementations are not feasible, includes the introductionof a venous catheter for dialysis via a large vein, usually one of theinternal jugular veins. Venous catheters are used either temporarily(usually for durations of weeks to months until a permanent accessdevelops) or permanently (usually lasts for a few months and up to ayear), and the dialysis path, from catheter entry point to the superiorvena cave, is prone to continuous stenoses. Therefore the need to verifyopen path for catheterization and maintain such a path opened forprolonged periods in an effective way that will include immediateopening of stenotic portions as well as an immediate follow upvisualization with minimal use of contrast media.

A dilatation balloon catheter for creating and/or visualizing a path fordialysis venous catheterization may include a high pressure balloon aspreviously described (e.g., dilating under pressures of 15 atmospheresor more) or alternatively may include a moderate pressure balloon (e.g.,dilating under 10 atmospheres or less), or a regular pressure balloon(e.g., dilating under atmospheres or less).

The following steps, at least in part, may be performed for venouscatheterization using exemplary balloon catheter according to thepresent disclosure (not necessarily in same order):

-   -   1. inserting a dilatation type balloon catheter into a large        vein, optionally internal jugular vein, optionally through a        vascular sheath, optionally over a guide wire and advancing it,        optionally guided under fluoroscopy, until reaching the blocked        or narrowed site in the central vein, optionally the        brachiocephalic vein;    -   2. inflating the balloon member of the catheter to dilate the        narrowed site (angioplasty);    -   3. while the balloon is being inflated and/or is maintained        inflated, injecting contrast enhancing material via the proximal        infusion exit port of the balloon catheter so it may flow in the        jugular and/or superior vena cava and/or other neck veins;    -   4. imaging (taking angiogram) veins to locate stenoses and/or        blocked areas;    -   5. if needed, placing a stent in a vein portion, optionally        excluding neck veins for extending potential use as central        venous access in the future;    -   6. deflating the balloon member;    -   7. injecting contrast enhancing material once more to image the        treated area, analyzing current condition and deciding if        further sessions are needed;    -   8. removing the balloon catheter and any other instrumentation        (such as guidewire and/or sheath).

Reference is made to FIGS. 10A-C which schematically illustrate stagesin a method for creating a venous catheterization path by first dilatinga narrowed brachiocephalic vein portion BCV and then performing animmediate follow up visualization in an internal jugular vein JV. Asshown in FIG. 10A, each brachiocephalic vein BCV is formed by the unionof internal jugular vein JV and subclavian vein SCV, and thebrachiocephalic veins are then joined to form the superior vena cave SVCwhich extends down to the right atrium RA of the heart. A commonpractice is to create a catheterization path, such as path PTH shown inFIG. 10A, that begins at an entry point in internal jugular vein JV(although other entry points may be used, such as in the subclavian, theaxillary vein or the femoral vein), followed into brachiocephalic veinBCV and optionally further into the superior vena cava SVC and rightatrium RA. As in the case of the exemplary illustrated restenosis,common stenoses occur at the brachiocephalic vein BCV, althoughangioplasty may be needed at other locations along a potential path.

As shown in FIG. 10B, exemplary balloon dilatation catheter 1000 (shownfor demonstrative purposes and can be replaced with catheter 100 orcatheter 2000, for example) is introduced and extended through thesubclavian vein SCV such that balloon 1200 is situated substantially inthe stenosis and infusion exit port 1140 is located in or adjacent theJV-SCV junction. Balloon catheter 1000 is optionally deployable in anover-the-wire approach along a previously introduced guidewire 1400which is extendable from guidewire opening 1160 at the distal tip ofelongated catheter body 1100 along guidewire lumen 1330 and out throughguidewire inlet port 1130 (not shown). Once in position, dilatationballoon 1200 may be inflated, optionally at moderate to high pressures,by pressurizing inflation media (e.g., saline) via inflation inlet port1120. After angioplasty, as illustrated in FIG. 10C, contrast medium isinfused via infusion exit port 1140 towards jugular vein JV andsubclavian vein SCV. At infusion, balloon 1200 may remain at leastpartially inflated or fully inflated substantially in the dilatationpressure.

Due to local anatomy and physiology of the JV-SCV junction and of thetwo veins, substantial amount or even most of the contrast medium willflow into jugular vein JV, hence relatively small volumes of contrastmedium 1500 are needed for accurate local imaging of the jugular vein JVin a way that may dramatically reduce radiation time and potential ofrenal damage due to contrast agents. Using imaging, the practicingphysician can visualize the effective length of jugular vein JV andentire catheterization path PTH, and may determine if and where isnecessary to place stents for facilitating openings at areas prone tonarrowing and restenosis.

Optionally, additionally or alternatively, other venous portions ofcatheterization path PTH are treated with angioplasty using balloon 1200instead or in addition to the brachiocephalic vein, and/or otherportions along path PTH can be chosen for occlusion during contrastmedium 1500 infusion, for example the superior vena cava SVC or evenupwards the natural blood stream direction.

Optionally, additionally or alternatively, medications are alsodelivered locally (not shown) using dilatation balloon catheter 1000,either drug eluting from outer surfaces of balloon 1200 and/or flowablemedications that are infused, optionally, via infusion exit port 1140with or without contrast medium 1500.

In an aspect of some embodiments, a dilatation balloon catheteraccording to the present disclosure is used for fibrin sheath balloondisruption procedures. Fibrin sheath is an inherent process happeningwith long term implanted dialysis catheters. It is a thin but strongtissue surrounding the catheter and preventing it from properfunctioning. Common treatments of fibrin sheath include stripping,thrombolysis, and balloon disruption. With balloon disruption, thecatheter is removed a special purpose dilatation balloon catheter isinserted and inflated such that the fibrin sheath is disrupted. Currentknown dedicated balloon disruption catheters and methods are consideredinefficient for imaging the fibrin sheath during and after disruption.

Reference is now made to FIGS. 11A-F which schematically illustratestages in a method for fibrin sheath disruption, in accordance with someembodiments of the present invention. FIG. 11A shows an exemplaryscenario of a first chronic dialysis catheter 3100 having its tippositioned in the superior vena cave SVC and fully surrounded with afibrin sheath FS as a consequence of prolonged implantation. In someembodiments, an exemplary dilatation balloon catheter 3300 (shown fordemonstrative purposes and can be replaced with catheter 100, catheter1000 or catheter 2000, for example, or be a dedicated variationthereof), comprising an elongated body 3310 enclosing at least twolumens capable of passing therethrough a guidewire, an infusion fluidand a balloon inflation fluid. Balloon catheter 3300 also includes adilatation balloon member 3320 and an infusion port 3330 locatedproximally to balloon member 3320. A guidewire inlet port 3340 allowsinsertion of a guidewire through balloon catheter 3300 for over-the-wiredelivering technique. Optionally, balloon member 3320 is inflatable to8-10 mm, or higher or lower, optionally is a high pressure balloon.

As shown in FIG. 11B, the first dialysis catheter 3100 is removed over aguidewire 3200 and in FIG. 11C dilatation balloon catheter 3300 isintroduced over same guidewire 3200 until positioning balloon member3320 adjacent a target location such as the distal end of the fibrinsheath FS. As shown in FIG. 11D balloon member 3320 is inflated withinthe fibrin sheath for disrupting it. Then (FIG. 11E), contrast enhancingmaterial CM is injected through infusion port 3330 into the fibrinsheath for enabling visualization of remaining sheath and for performingof additional angioplasty if needed. Thrombolytic agents may also bedispersed via infusion port 3330 or through a different port (notshown). Balloon member 3320 may be optionally deflated and positionedadjacent other portions of the fibrin sheath as needed (not shown) andoptionally other flushing of contrast materials may be performed forfurther verifications. The contrast enhancing material CM may bedispersed such that to allow visualization substantially beyond thefibrin sheath for visualizing other vasculature portions such as theinternal jugular vein JV for example in order to see if it is patent forfuture access and catheter placement. After proper disruption of thefibrin sheath, imagery verifications and other treatment steps asneeded, balloon catheter 3300 can be removed and replaced with a second(new) dialysis catheter 3400.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

What is claimed is:
 1. A method for disrupting a fibrin sheath from a host blood vessel and enhancing visualizing thereof, the method comprising: removing a first dialysis catheter from the host blood vessel; introducing a dilation balloon catheter into the host blood vessel wherein said dilation balloon catheter comprises a dilatation balloon, an infusion lumen, and a lateral infusion opening in said infusion lumen that is positioned proximal to said dilatation balloon; positioning said dilatation balloon adjacent to a target location associated with boundaries of the fibrin sheath; inflating said dilatation balloon so as to disrupt the fibrin sheath and occlude said host blood vessel; injecting contrast enhancing material through said lateral infusion opening and into the fibrin sheath while said dilatation balloon is inflated and is occluding the host blood vessel for enabling visualization of remaining portions of said fibrin sheath; verifying fibrin sheath disruption using imagery; and replacing said dilation balloon catheter with a second dialysis catheter.
 2. The method of claim 1, wherein the host blood vessel is a superior vena cava.
 3. The method of claim 1, wherein said removing includes removing said first dialysis catheter over a guidewire.
 4. The method of claim 1, wherein said dilation balloon catheter comprises an inflation lumen for passing therethrough a balloon inflation fluid.
 5. The method of claim 1, wherein said lateral infusion opening is located proximally adjacent to said dilation balloon.
 6. The method of claim 1, further comprising: dispersing thrombolytic agents via said dilation balloon catheter.
 7. The method of claim 1, further comprising: deflating said dilatation balloon; repositioning said dilation balloon adjacent a different portion of the fibrin sheath; and repeating at least one of said inflating, said injecting, and said verifying.
 8. The method of claim 1, comprising: flushing said contrast enhancing material to disperse beyond the fibrin sheath; and visualizing vasculature portions other than the host target vessel, including internal jugular vein.
 9. The method of claim 1, wherein said infusion lumen comprises a proximal opening and a distal opening that is distal to said dilatation balloon, and wherein said method further comprises: inserting a guidewire into the host blood vessel; and wherein said introducing is performed when said guidewire extends in said infusion lumen from said distal opening to said proximal opening.
 10. The method of claim 9, wherein said guidewire blocks a portion of said infusion lumen sized and shaped as external boundaries of said guidewire, such that said injecting causes said contrast enhancing material to exit mainly or only through said lateral infusion opening.
 11. The method of claim 1, wherein a valving mechanism is provided in said infusion lumen distal to said lateral infusion opening, wherein said injecting follows operating the valving mechanism such that said injecting causes said contrast enhancing material to exit mainly or only through said lateral infusion opening. 